9. Recent Publications (Some) 1: Otolaryngol Head Neck Surg. 2004 Dec;131(6):797-803. Related Articles, Links The role of oxidants and antioxidants in otitis media with effusion in children. Yilmaz T, Kocan EG, Besler HT, Yilmaz G, Gursel B. Objective Determine the possible role of oxidants and antioxidants in the pathogenesis of otitis media with effusion in children. Study design and setting Randomized controlled trial, tertiary referral center. The study group was made up of children with otitis media with effusion who were to undergo bilateral ventilation tube insertion and adenoidectomy. The control group was comprised of otherwise healthy children. The blood levels of antioxidants (retinol, beta-carotene, alpha-tocopherol, laycopene, ascorbic acid, superoxide dismutase, glutathione peroxidase, GSH) and oxidation products (malondialdehyde) were determined before and 1 month after the operation in the study group and once only in the control group. These substances were also measured in the adenoid tissue and middle ear fluids. Results In the study group, the blood levels of antioxidants and oxidants before and after the operation were significantly different when compared with the control group ( P < 0.05). In the study group, the blood antioxidant levels increased and oxidant levels decreased significantly after the operation ( P < 0.05). The levels after the operation never reached those of the control group. Conclusions and significance Oxidants and antioxidants played a significant role in the pathogenesis of otitis media with effusion in children. These children are under significant oxidative stress. Insertion of a ventilation tube and adenoidectomy significantly decreased the oxidative stress in these patients, but could not normalize it completely. Additional studies are necessary in the clinical use of antioxidants in otitis media with effusion. PMID: 15577771 [PubMed - in process] 2: Ulus Travma Derg. 2004 Jul;10(3):149-59. Related Articles, Links [The role of nitric oxide in trauma and infection] [Article in Turkish] Kuyumcu A, Duzgun AP, Ozmen MM, Besler HT. Department of Nutrition and Dietetics, School of Health Technology, Hacettepe University, Ankara, Turkey. Nitric oxide (NO) is a very important molecule for homeostasis. It is involved in several pathological conditions ranging from hypertension to septic shock. It is synthesized from L-arginine, which is catalyzed by nitric oxide synthase (NOS). Both constitutional and inducible NOS are involved in NO synthesis. While NO produced by constitutional NOS is required for normal physiologic processes, excessive production by inducible NOS results in injury and tissue damage. Induced NO may be either protective or damaging in acute inflammatory conditions. As a result of pluripotent activities, NO presents as a paradoxical phenomenon in almost all conditions in which confusing aspects arise concerning the pathophysiology. This article reviews the role of NO in trauma and infections. PMID: 15286885 [PubMed - in process] 3: Int J Pediatr Otorhinolaryngol. 2004 Aug;68(8):1053-8. Related Articles, Links The role of oxidants and antioxidants in chronic tonsillitis and adenoid hypertrophy in children. Yilmaz T, Kocan EG, Besler HT. Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Hacettepe University, Hacettepe Ankara, Turkey. taneryilmaz@yahoo.com OBJECTIVE: To determine the possible role of oxidants and antioxidants in the pathogenesis of chronic tonsillitis (CT) and adenoid hypertrophy (AH) in children. METHODS: Randomized, prospective, controlled. The study group was made up of children with chronic tonsillitis and adenoid hypertrophy who are to undergo tonsillectomy and adenoidectomy. The control group was constructed with otherwise healthy children with normal ENT examination. The blood levels of antioxidants (retinol, beta-carotene, alpha-tocopherol, laycopene, ascorbic acid, superoxide dismutase, glutathione peroxidase, GSH) and peroxidation products (malondialdehyde) were determined before and 1 month after the operation in the study group and once only in the control group. These antioxidants and peroxidation products were also measured in the tonsil and adenoid tissue that were obtained during operation. RESULTS: In the study group, the blood levels of antioxidants and oxidant before and after the operation were significantly different when compared to the control group (P < 0.05). In the study group, the blood antioxidant levels increased and oxidant level decreased significantly after the operation (P < 0.05). These levels after the operation never reached those of the control group. CONCLUSIONS: Oxidants and antioxidants played a significant role in the pathogenesis of chronic tonsillitis and adenoid hypertrophy in children. These children are under significant oxidative stress. Tonsillectomy and adenoidectomy significantly decreased the oxidative stress in these patients, but could not normalize it completely. Further studies are necessary to evaluate their possible therapeutic role in preventing recurrent tonsillitis and treating postoperative patients to help normalize their blood levels of antioxidants. PMID: 15236892 [PubMed - in process] 2 4: Hepatogastroenterology. 2004 Mar-Apr;51(56):401-7. Related Articles, Links The effects of verapamil vs. allopurinol on intestinal ischemia/reperfusion injury in rats. "An experimental study". Kulah B, Besler HT, Akdag M, Oruc T, Altinok G, Kulacoglu H, Ozmen MM, Coskun F. Ankara Numune Teaching and Research Hospital 3rd Surgical Clinic, Turkey. BACKGROUND/AIMS: Although studies have reported that xanthine oxidase inhibitors or calcium channel blockers attenuate the ischemia-reperfusion injury in several organ systems, no comparative study exists on the significance of each of these pathways. To study this, in anesthetized Wistar Albino rats, a surgical model for intestinal ischemia-reperfusion injury was employed. METHODOLOGY: In experimental animals, after laparotomy, the superior mesenteric artery was occluded for 30 min, followed by a 2-h period of reperfusion; control rats underwent only a sham laparotomy procedure. One group of experimental animals was pretreated intraperitoneally with the calcium channel blocker verapamil (0.3 mg/kg), another group with the xanthine oxidase inhibitor allopurinol (100 mg/kg), the third group received no pretreatment. Plasma lactate, malondialdehyde and glutathione levels as well as intestinal tissue malondialdehyde and glutathione levels were measured to assess for possible protective effects. Histologic evaluation of the extent of injury was also performed. RESULTS: Irreversible tissue damage was depicted in the untreated group, and partially in the allopurinol pretreatment group by histologic examination. Ischemia-reperfusion injury was reversible in the verapamil group. The laboratory results also supported these findings. CONCLUSIONS: Protective effects of verapamil on ischemia-reperfusion injury have been found to be significantly (p<0.0001) more effective compared to allopurinol. PMID: 15086169 [PubMed - indexed for MEDLINE] 5: Hepatogastroenterology. 2003 Nov-Dec;50(54):2127-32. Related Articles, Links Comparison of the effects of continuous and intermittent portal triad occlusion (PTO) in rats. Ozmen MM, Oruc MT, Besler HT, Kulah B, Safali M, Polat A, Ozer V, Coskun F. Department of Surgery Ankara Numune, Teaching and Research Hospital, Ankara, Turkey. mmahir@excite.com BACKGROUND/AIMS: It has previously been shown that prolonged ischemia of the liver had a mortal course and a method of intermittent occlusion of the hepatic pedicle was defined in order to minimize the damage to the liver. The present experimental study aimed to compare the effects of continuous and intermittent occlusion of the 3 hepatic pedicle on the liver by measuring serum lactate, serum MDA malondialdehyde and glutathione levels and by evaluating the histologic changes in the liver tissue. METHODOLOGY: Thirty male Wistar albino rats weighing 300 +/- 50 g were divided into three groups of ten animals. Group 1 underwent a sham operation. Animals in group 2 underwent continuous portal triad occlusion (PTO group) for 30 minutes following laparotomy. The remaining ten animals in group 3 underwent intermittent occlusion consisting of 10 minutes of occlusion followed by 10 minutes of reperfusion for a total period of 30 minutes of ischemia. Blood samples were collected at the 1st and 6th postoperative hour for analytical evaluation. After sacrificing the animals, liver samples were obtained for histologic evaluation. RESULTS: The serum lactate levels were significantly higher in both portal triad occlusion groups than in the control at the 1st hour. While lactate levels also increased at the 6th hour in the continuous PTO group, it decreased to the level of control values in the intermittent PTO group. The difference between continuous and intermittent groups was also significant. Despite the unchanged malondialdehyde levels in the control group, malondialdehyde levels were significantly increased at the first and sixth hour in both PTO groups and the levels were also significantly higher than control values. Malondialdehyde levels of intermittent PTO groups at the first and sixth hour were both significantly lower than continue PTO groups. Whole blood glutathione levels were not changed in control groups with time, levels increased significantly in both PTO groups. Glutathione levels were higher than control values in both PTO groups at the first hour. While it turned to its basal value in intermittent PTO groups at the 6th hour, it was still significantly higher in the continuous PTO group. When both PTO groups were compared, glutathione levels were found to be significantly higher in the continuous group both at the first and sixth hour than in the intermittent PTO group. Histopathologic evaluation also showed that there was less damage in the intermittent PTO group than in the continuous PTO group. CONCLUSIONS: Our results show that continuous portal triad occlusion resulted in significant oxidative stress and cell damage as confirmed by increased serum lactate and blood malondialdehyde levels. The blood glutathione levels are increased due to a greater requirement in response to increased oxidative stress induced by portal triad occlusion. It is also confirmed that intermittent portal triad occlusion is safer as it causes less oxidative stress and cell damage so that its use is strongly suggested whenever portal triad occlusion is required. PMID: 14696479 [PubMed - indexed for MEDLINE] 6: Nutr Neurosci. 2003 Jun;6(3):189-96. Related Articles, Links Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Besler HT, Comoglu S. Department of Nutrition and Dietetics, Division of Nutritional Sciences, School of Health Technology, Hacettepe University, Sihhiye, 06100-Ankara, Turkey. htbf@hacettepe.edu.tr Free radical-mediated peroxidation of biological molecules, especially of lipids, is 4 implicated in the pathogenesis of a number of diseases like multiple sclerosis. Low concentration of antioxidant vitamins: beta carotene, retinol, alpha tocopherol and ascorbic acid have been observed in serum or cerebrospinal fluid of multiple sclerosis patients. On the basis of these observations, we studied the potential lipoprotein oxidation and total antioxidant capacity in the pathogenesis of multiple sclerosis. Lipoprotein oxidizability for plasma in vitro, serum levels of autoantibodies against oxidized low-density lipoproteins, plasma total homocysteine levels with vitamin B12 and folate, and plasma total antioxidant capacity were measured in twenty four patients with multiple sclerosis and twenty four healthy sex- and age-matched person as control. In multiple sclerosis patients during an attack, a significant increase in both in vitro lipid oxidizability for plasma and in the levels of autoantibodies against oxidized low-density lipoproteins, and a strong decrease in plasma total antioxidant capacity were detected. Plasma total homocysteine levels were significantly higher in multiple sclerosis patients whose plasma vitamin B12 and folate levels were lower but not statistically significant, than controls. The present study indicates that lipoprotein oxidation may be important factor in the course of multiple sclerosis and in vitro measurements of plasma oxidation kinetics as an indication for lipoprotein oxidation might be useful as an additional tool for the clinical diagnosis of multiple sclerosis. PMID: 12793524 [PubMed - indexed for MEDLINE] 7: Clin Nutr. 2003 Jun;22(3):277-81. Related Articles, Links The effect of immunonutrition on bacterial translocation, and intestinal villus atrophy in experimental obstructive jaundice. Zulfikaroglu B, Zulfikaroglu E, Ozmen MM, Ozalp N, Berkem R, Erdogan S, Besler HT, Koc M, Korkmaz A. Department of Surgery, Ankara Numune Teaching and Research Hospital, 06100 Ankara, Turkey. BACKGROUND & AIMS: Spontaneous bacterial infection and septicemia due to increased bacterial translocation (BT) in patients with obstructive jaundice result in significant morbidity and mortality. The present study evaluates the effects of enteral nutrition with immune enhancing feeds on BT and intestinal villus histopathology promoted by obstructive jaundice. METHODS: Fifty male Wistar-albino rats weighing 250-300g were assigned into five equal groups of 10. Animals in Groups I, II, and III were fed with standard chow, those in Group IV were given glutamine 1g/kg/day and the remaining 10 animals in Group V were fed with an arginine, omega-3 fatty acids, and RNA-supplemented enteral diet for (1g/kg/day amino acid and 230 kcal/kg) 7 days preoperatively. Group I underwent sham operation and the remaining animals in all other groups underwent common bile duct ligation. After operation, Group I had standard chow, Groups II and IV had glutamine, Groups III and V had an arginine omega-3 fatty acids, and RNA-supplemented enteral diet for 7 days. All animals were sacrificed on the 8th postoperative day and evaluated both biochemically and histopathologically. Samples from blood, liver, mesenteric lymph nodes and spleen were cultured under aerobic conditions. RESULTS: Significantly 5 less BT was observed in groups fed with an arginine, omega-3 fatty acids, and RNAsupplemented enteral diet or glutamine in pre-and postoperative periods as compared to others (P<0.001). Histologic evaluation also showed significant reduction in villus atrophy in these groups. CONCLUSIONS: Enteral immunonutrition using glutamine or arginine, omega-3 fatty acids, and RNA-supplemented enteral diet during both preand postoperative periods seems to reduce BT and decrease atrophy of intestinal mucosal villi in rats with obstructive jaundice. PMID: 12765668 [PubMed - indexed for MEDLINE] 8: Nutr Neurosci. 2002 Jun;5(3):215-20. Related Articles, Links Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis. Besler HT, Comoglu S, Okcu Z. Department of Nutrition and Dietetics, School of Health Technology, Hacettepe University, Sihhiye, Ankara, Turkey. htbf@hacettepe.edu.tr We determined serum levels of ascorbic acid, betacarotene, retinol and alpha tocopherol and lipid peroxidation (as estimated by thiobarbituric acid reacting substances (TBARS) generation) in 24 multiple sclerosis (MS) patients and 24 healthy sex- and age-matched person as control. The levels of four antioxidant vitamins were significantly lower in MS patients compared to controls (p < 0.05). TBARS levels were significantly higher in the patients of MS compared to the controls (p = 0.001). In MS patients, the levels of beta-carotene, alpha tocopherol and ascorbic acid correlated significantly with each other (r2 = 0.689 - 0.779). It appeared that there was inverse correlation between the serum levels of ascorbic acid or beta-carotene, but not of alpha tocopherol or retinol, and TBARS levels in MS. The present study indicates that antioxidant vitamins (alpha tocopherol, beta-carotene, retinol and ascorbic acid) are decreased in sera of MS patients during an attack, and that this decrease may well be dependent on the increased oxidative burden as reflected by lipid peroxidation products. The role of antioxidant vitamin supplementation in prevention and/or treatment of MS remains to be explored. PMID: 12041878 [PubMed - indexed for MEDLINE] 6 9: Surg Endosc. 2002 Mar;16(3):468-71. Epub 2001 Nov 16. Related Articles, Links Comment in: Surg Endosc. 2003 Aug;17(8):1337; author reply 1338. Does splanchnic ischemia occur during laparoscopic cholecystectomy? Ozmen MM, Kessaf Aslar A, Besler HT, Cinel I. Department of Surgery, Ankara Numune Teaching and Research Hospital, Talatpasa Bul., 06100, Ankara, Turkey. mmahir@excite.com BACKGROUND: Although it has been been shown that the elevation of abdominal pressure causes splanchnic ischemia, the pathophysiological changes that occur during laparoscopic cholecystectomy are still under investigation. Our aim was to evaluate the changes in nitric oxide (NO), malondialdehyde (MDA), and gastric intramucosal pH (pHi) during laparoscopic surgery to verify whether splanchnic ischemia had occurred. METHODS: Forty patients (11 men and 29 women) scheduled for cholecystectomy were randomly divided to undergo either open (OC) or laparoscopic cholecystectomy (LC). Repeated blood samples were collected for the measurement of NO and MDA concentrations. End-tidal carbon dioxide (ETCO2) levels were measured using a capnograph, and pHi was assessed using a tonometric nasogastric catheter. RESULTS: Although no significant change in pH was observed in the LC group during the procedure, it decreased significantly in the OC group and then returned to normal immediately after the procedure. ETCO2 did not change in the LC group but it increased in the OC group. Although it was not statistically significant, NO concentrations were slightly increased in the LC group. The same magnitude of increase was seen in MDA levels but it was not significant. Neither NO nor MDA levels changed in the OC group. CONCLUSION: LC has no adverse effects on gut perfusion. Even if the abdominal organs are hypoperfused during the procedure, compensates for this hypoperfusion so that it pulsatile NO secretion does not cause any harm. Since LC is a short procedure, the significance of these events for extended procedures still needs to be clarified. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 11928030 [PubMed - indexed for MEDLINE] 7 10: Clin Sci (Lond). 1995 Jan;88(1):59-66. Related Articles, Links Comparison of the modulatory influence of maize and olive oils and butter on metabolic responses to endotoxin in rats. Besler HT, Grimble RF. Department of Human Nutrition, School of Biological Sciences, University of Southampton, U.K. 1. n-3 polyunsaturated fatty acids decrease responses to cytokines and inflammatory agents. The present study examines how different intakes of n-6 and n-9 fatty acids influence the metabolic response to endotoxin in Wistar rats. 2. Weanling male rats were, for 4 weeks, fed diets containing 50, 100 or 200 g/kg fat in the form of maize oil (rich in linoleic acid), butter (poor in linoleic acid, rich in oleic acid) or olive oil (adequate in linoleic acid, rich in oleic acid) or standard laboratory chow. All butter and olive oil diets included 10 g/kg maize oil, in total fat, to avoid essential fatty acid deficiency. 3. Rats subsequently received 800 micrograms/kg Escherichia coli endotoxin or sterile saline subcutaneously. Twenty-four hours after injection, the rate of tissue protein synthesis was measured in liver, lung, kidney, tibialis muscle and spleen by the 'flooding dose' method. Protein and zinc concentrations were assayed in all tissues and serum albumin and caeruloplasmin measured. 4. In animals fed chow, protein synthetic rate increased by 18%, 29% and 27% in liver, lung and kidney respectively. Tissue zinc concentrations increased by 33% in kidney, and tissue protein increased by 17%, 23% and 17% in liver, lung and kidney respectively. Serum caeruloplasmin increased by 60% and albumin concentration fell by 14%. 5. In animals consuming the 50 g/kg maize oil diet, protein synthetic rate increased by 56%, 36% and 34% in liver, lung and kidney respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID: 7705002 [PubMed - indexed for MEDLINE] 11: Laryngoscope. 2004 Jul;114(7):1200-3. Related Articles, Links Role of free radicals and antioxidants in nasal polyps. Dagli M, Eryilmaz A, Besler T, Akmansu H, Acar A, Korkmaz H. Department of Otolaryngology and Head and Neck Surgery, Ankara Numune Hospital, Ankara, Turkey. OBJECTIVES/HYPOTHESIS: The aim of this study is to determine the role of free radicals and antioxidants in nasal polyps. STUDY DESIGN: Prospective, randomized, controlled study. METHODS: Thirty-one patients with nasal polyposis and a control group consisting of 19 patients with septal deviation and lower turbinate hypertrophy were included in the study. Levels of the antioxidants retinol, beta-carotene, alphatocopherol, and ascorbic acid were measured from the sera of the patients with nasal polyposis and the control group. Plasma levels of superoxide dismutase activity (SOD), glutathione peroxidase (GSHPX) activity, and reduced glutathione (GSH) 8 were also obtained. As a peroxidation product, the levels of the malondialdehydethiobarbituric acid (MDA) combination were measured from the plasma of patient and control groups. Measurements of MDA, GSH, and alpha-tocopherol levels were also taken from the polyp tissue and turbinate mucosa of the control group. RESULTS: The blood levels of antioxidants and MDA as an oxidant were significantly different in the patient group compared with the control group (P <.01). The tissue levels of antioxidants and MDA were significantly different in the patients with polyposis compared with the control group (P <.01). The blood and tissue anti-oxidant levels were found to be decreased, and MDA levels as an oxidant increased significantly in the patient group with polyposis when compared with the control group, and there was a negative correlation between oxidative stress and antioxidants. CONCLUSION: This study demonstrates that oxidative stress and tissue and blood antioxidants in the patients with polyposis were significantly different compared with the control group. The blood and tissue antioxidant levels decreased, and MDA levels, as an oxidant, increased significantly in the patient group with polyposis when compared with the control group. The current study demonstrates that there is strong evidence related to oxidative stress in the pathogenesis of nasal polyposis, and antioxidants can have a preventive role in free-radical-mediated tissue damage in nasal polyposis. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 15235348 [PubMed - indexed for MEDLINE] 12: Int J Exp Diabetes Res. 2002 Apr-Jun;3(2):119-30. Related Articles, Links Hydrogen peroxide-induced inhibition of vasomotor activity: evaluation of single and combined treatments with vitamin A and insulin in streptozotocin-diabetic rats. Zobali F, Besler T, Ari N, Karasu C; (Antioxidants in Diabetes-Induced Complications) The ADIC Study Group. Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan, Turkey A positive correlation has been established between increased oxidative stress and cardiovascular diseases in diabetes mellitus. We evaluated the effects of single or combined treatments with vitamin A (retinol acetate, 30 mg/kg/day, for 12-weeks) and insulin (8-10 IU/rat/day for the final 6-week) on vasomotor activity, oxidative stress and retinol metabolism in 12-week streptozotocin diabetic rats. The vasomotor activity was determined by measuring in vitro responsiveness of aorta rings to phenylephrine (PE) and acetylcholine (ACh) in the absence or in the presence of hydrogen peroxide (H2O2). Preincubation with H2O2 (10 microM) produced a significant decrease in PE (1 mM)-induced contraction in untreated-diabetic but not in control rats. Single 9 treatment with insulin counteracted this effect of H2O2 and also reversed the increased contractile response of diabetic aorta to PE, while vitamin A was found to be ineffective. H2O2 (10 microM) also inhibited ACh (1 mM)-stimulated endotheliumdependent relaxation two fold more in diabetic than in control aorta. In the prevention of H2O2-induced inhibition of vascular relaxation to ACh, vitamin A alone was markedly effective while insulin alone was not. The combination of vitamin A plus insulin removed the inhibitory action of H2O2 in diabetic aorta. Diabetic animals displayed an increased level of aorta thiobarbituric acid reactive substance (TBARS) in association with decreased levels of plasma retinol and retinol-binding protein (RBP). Single treatment with insulin, in spite of allowing recovery of normal growth rate and improved glucose and retinol metabolism in diabetic rats, was unable to control TBARS production to the same extent as vitamin A alone. Our findings suggest that the maintenance of ACh-stimulated endothelium-dependent vasorelaxant tone in normal physiological levels depends largely on the prevention and/or inhibition of peroxidative stress, which is achieved by combined treatment with vitamin A plus insulin. The use of vitamin A together with insulin provides a better metabolic control and more benefits than use of insulin alone in the reduction of diabetes-induced vascular complications. PMID: 11991198 [PubMed - indexed for MEDLINE] 13: Turk J Pediatr. 2000 Jan-Mar;42(1):17-21. Related Articles, Links Serum levels of antioxidant vitamins (alpha tocopherol, beta carotene, and ascorbic acid) in children with bronchial asthma. Kalayci O, Besler T, Kilinc K, Sekerel BE, Saraclar Y. Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. We determined serum levels of alpha tocopherol, beta carotene, and ascorbic acid and lipid peroxidation products (thiobarbituric acid reactive substances--TBARS) in 14 children during an asthma attack and remission. Twelve healthy children served as controls. All antioxidant vitamins were significantly lower in asthmatics at remission compared to controls. Comparison of attack and remission periods in asthmatic patients failed to reveal any difference except in beta carotene (p = 0.03). The levels of all three vitamins correlated very significantly with each other (r = 0.89-0.95). TBARS levels were significantly higher at asthma attack compared to remission (p = 0.001). No correlation was observed between the antioxidant vitamins and lipid peroxidation products. This study shows that antioxidant vitamins are decreased in sera of asthmatic patients even during the asymptomatic periods of the disease, and that this decrease is not totally dependent on the increased oxidative stress as reflected by lipid peroxidation products. The role of antioxidant vitamins in prevention and/or treatment of asthma remains to be determined. PMID: 10731863 [PubMed - indexed for MEDLINE] 14: J Allergy Clin Immunol. 2006 Nov;118(5):1097-104. Links Oxidative stress and genetic and epidemiologic determinants of oxidant injury in childhood asthma. 10 Ercan H, Birben E, Dizdar EA, Keskin O, Karaaslan C, Soyer OU, Dut R, Sackesen C, Besler T, Kalayci O. Pediatric Allergy and Asthma Unit, School of Medicine, Pediatric Allergy and Asthma Unit, Hacettepe, Ankara, Turkey. BACKGROUND: The factors contributing to the oxidant/antioxidant imbalance in asthma are incompletely understood. OBJECTIVE: To determine the factors associated with oxidative stress including asthma severity and the genotype of the antioxidant enzymes. METHODS: A total of 196 children with mild asthma, 116 children with moderate-severe asthma, and 2 healthy control groups (187 and 68 children) were included in the study. Plasma levels of malondialdehyde were measured as the indicator of oxidative stress, and reduced glutathione levels as the indicator of antioxidant defense. Children were genotyped for null variants of glutathione S transferase (GST) T1 and GSTM1, and ile105val variant of GSTP1. Risk factors were analyzed with multivariate logistic regression. RESULTS: Systemic levels of malondialdehyde increased and reduced glutathione levels decreased significantly from healthy controls to patients with mild asthma and then to patients with moderate-severe asthma (P < .001 for each). Multivariate logistic regression identified asthma and asthma severity as independent factors associated with oxidative stress (odds ratio between 17 and 56; P < .001). Children with asthma with GSTP1 val/val genotype had higher malondialdehyde and lower glutathione levels compared with other genotypes (P = .023 and P = .014, respectively). GSTP1 val/val genotype was independently associated with asthma severity (odds ratio, 4.210; 95% CI, 1.581-11.214; P = .004). CONCLUSION: Our study indicates the presence of a strong oxidative stress in children with asthma that increases with the severity of the disease. In this population, val/val genotype at GSTP1 ile105val locus may be an important factor in determining the degree of oxidant injury. CLINICAL IMPLICATIONS: Children with asthma with val/val genotype at GSTP1 ile105val locus may be good candidates for supplemental antioxidant therapy. PMID: 17088135 [PubMed - indexed for MEDLINE] 11